The present invention relates to a process for the preparation of an optically active azabicyclo heptanone derivative of general Formula III 
wherein R1=H, X=CH2, Yxe2x80x94Z=xe2x80x94CHxe2x95x90CHxe2x80x94, from a racemic mixture of the xcex3-lactams of Formula (I) 
wherein R2 is H or COR3, (R3 is C1-4 alkyoxy, aryl or aryloxy),
Xxe2x80x2 is O or CHR4 (R4 is F, OH, Br, or H).
Yxe2x80x2xe2x80x94Zxe2x80x2 is CHxe2x95x90CH, 
or xe2x80x94CH(R6)CH2xe2x80x94 (R6=Br, OH, PhCH2O, or N3,
The present invention also relates to a process for the preparation of an optically active azabicyclo heptanone derivative of general Formula III wherein R1=H, Xxe2x80x2=CH2, Yxe2x80x2xe2x80x94Zxe2x80x2=CHxe2x95x90CH2 is useful as an intermediate in the synthesis of antiviral agents.
Carbocyclic analogues of purines are known as antiviral and anti neoplastic agents. For example the compound of Formula II is described as having potent activity against human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) (EP 0434450). 
wherein R5=Cyclopropylamino, or N-Cyclopropyl, N-Methylarnine.
Prior art discloses the preparation of 9-substituted-2-amino purines starting from a pyrimidine compound, coupling with enantiomerically pure sugar/carbocyclic analogues residue and cyclization to form the imidazole ring followed by introduction of suitable 6-substituent (PCT/GB95/00225). Carbovir and known analogues are prepared from the known xcex3-lactam (Vince lactam) 2-azabicyclo[2,2,1]hept-5-en-3-one (Formula I) wherein Xxe2x80x2 is xe2x80x94CH2, xe2x80x94Yxe2x80x2xe2x80x94Zxe2x80x2xe2x80x94 is xe2x80x94CHxe2x95x90CHxe2x80x94 and R2 is H.
Prior art indicates that the final product or any intermediate or starting material may be resolved by known methods or the racemic mixture of the product may be enzymatically converted to chirally pure compound. The xcex3-lactam can be prepared by reacting cyclopentadiene with tosylcyanide, (Vince J. Org. Chem. 1978, 43, 2311).
There are several synthetic pathways where chemical resolution into the enantiomer has been effected but the enzymatic resolution of xcex3-lactam will be the most economical commercial process. xcex3-lactamase methodology has been reported based on enantio-complementary biotransformation. Enzymatic resolution of bicyclic lactam using whole cell cultures ENZA1 and ENZA2 has been reported to give both the optical forms of lactam (S. V. Teylor, J. C. S. Chem. Comm., 1121, 1990, Tet. Assy., 4, 1117-1128). The detailed process has been described in patent (EP 0424064). The racemic lactam was treated with ENZA-xc2xd cell free extract at 30xc2x0 C. with shaking for 14 days. The crude (+)/(xe2x88x92) lactam was isolated by extraction with dichloromethane and purified by column chromatography on silica gel to provide the (+) lactam with 88% optical purity, ee, and the (xe2x88x92) lactam with 98% ee, optical purity.
Enzymatic resolution of N-Acyl bicyclic lactam using acylase has been described in patent (PCT/EP99/04814) in 31% yield with 98% ee. The conversion of the optically active N-Acetyl-lactam to (+)/(xe2x88x92) lactam is tedious.
The prior art methods to the cyclopentane moiety of carbocyclic nucleosides starting from non-carbohydrate synthons or readily available meso compounds generally involve a number of steps, which are often difficult to perform and provide poor yields, making the practical scale-up of these processes difficult and uneconomical.
The main object of the present invention is to provide a process for the preparation of an optically active azabicyclo heptanone derivative which obviates the drawbacks of the prior art processes and use cheaper and easily available microbial whole cell enzyme.
It is another object of the invention to provide a process for the preparation of (xe2x88x92) 2-Azabicyclo[2,2,1]-hept-5-ene-3-one Formula III, which is economical and efficient.
The present invention provides a process for the preparation of optically active azabicyclo heptanone derivatives using lactamases that will react with racemic xcex3-lactam of Formula I to give a single enantiomer of lactam (III) and the corresponding ring opened compound of formula (IV) in an enantiomerically pure form. 
Accordingly, the present invention provides a process for the preparation of (xe2x88x92)2-Azabicyclo[2,2,1]-hept-5-ene-3-one Formula III wherein R1=H, X=CH2, Yxe2x80x94Z=xe2x80x94CHxe2x95x90CHxe2x80x94, 
which comprises reacting a racemic mixture of a compound of Formula I: 
wherein R2 is H or COR3, (R3 is C1-4 alkoxy, aryl or aryloxy),
Xxe2x80x2 is O or CHR4 (R4 is F, OH, Br, or H),
Yxe2x80x2xe2x80x94Zxe2x80x2 is CHxe2x95x90CH, 
or xe2x80x94CH(R6)CH2xe2x80x94 (R6=Br, OH, PhCH2O, or N3,
with an enzyme, a lactamase or the whole cells of a microorgnism in a buffer containing organic solvent at temperature ranging between 25-30xc2x0 C. for a period ranging from 14 to 24 hr., extracting the mixture into an organic solvent, separating the organic layer and removing the organic solvent to obtain the product.
In one embodiment of the invention the microorganisms or enzymes used are selected from Bacillus, Klyuvera or Eschericha.
In another embodiment of the invention the whole cell is obtained from growing a culture of Klyuvera Citrophila, ATCC No.21285 (American Tissue and Type Culture, Box 1549, Manassas, Va. 20108), in a conventional culture medium.
In another embodiment of the invention, the cell extract or enzyme used comprises an enzyme or a cell extract from Klyuvera sp. (ATCC No.21285).
In another embodiment of the invention the buffer used is selected from the group consisting of phosphate buffer (0.05 M-0.1 M, 6-8 pH), citrate buffer (0.05 M-0.1 M 6-7.5 pH) and Trisbuffer (0.05M-0.2M, 7-8 pH).
In another embodiment of the invention the buffer used comprises phosphate buffer (0.2 M, 7.4 pH).
In another embodiment of the invention the organic solvent used for the reaction along with buffer is selected from the group consisting of alcohols, alkyl acetates, ketones and sulfoxides.
In a further embodiment of the invention, the organic solvent is selected from the group consisting of methanol, ethanol, butanol, ethyl acetate, acetone, dimethyl sulfoxide and dimethylformamide.
In a further embodiment of the invention, the organic solvent comprises acetone.
In another embodiment of the invention the percent of organic solvent used for the reaction along with buffer is in the range of 5% to 50% (v/v).
In another embodiment of the invention the percent of organic solvent used for the reaction along with buffer comprises is 10%(v/v).
In another embodiment of the invention the solvent used for extraction comprises a chlorinated solvent selected from the group consisting of chloroform, ethylene dichloride, methylene dichloride and an alkyl acetate.
In another embodiment of the invention, the alkyl acetate used as the solvent for extraction comprises ethyl acetate.
In another embodiment of the invention the solvent used for extraction comprises methylene chloride.
In a feature of the invention the chemical yield (xe2x88x92) 2-Azabicyclo[2,2,1]-hept-5-ene-3-one is 39.3% and the optical purity is 98%.